This continuation grant will attempt to identify factors important in the development of ventricular hypertrophies, mainly due to exercise and systolic overload either alone and combined. Renal hypertension and chronic swimming in the female rat will be the predominant interventions. We will explore why swimming results in cardiac hypertrophy and increased cardiac myosin isoenzyme v1, while running does not. Hemodynamics, hormones and blood gasses wil be investigated. The biochemistry of cardiac contraction and relaxation will be explored by studying sarcoplasmic reticulum and troponin-tropomyosin. Male and females will be investigated with gonadectomy and sex hormone cross-over studies, to explore why females respond with cardiac hyertrophy to swimming and males do not. The role of diastolic overload, unrelated to exercises, will be explored in combined ventricular hypertrophies using rats with arterivenous fistula. The role of catecholamines in the development of cardiac hypertrophy and the training effect will be studied in rats subjected to chronic dobutamine treatment. The effect of systolic loads, other than renal hypertension, will be investigated, including DOCA-salt hypertension (a low renin, high blood volume form of hypertension) and myocardial infarction (a different type of load) combined with swimming. Senescent rats will be exposed to hypertension and exercise to determine if their hearts respond to combined hypertrophy similarly or differently than hearts of adult rats.